ArticlePloS one2015
8-Chloroadenosine Sensitivity in Renal Cell Carcinoma Is Associated with AMPK Activation and mTOR Pathway Inhibition.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- 8-Chloroadenosine suppresses hepatocellular carcinoma progression via ADAR1/PPARγ axis-mediated lipid metabolism.Genes & diseases · 2026Article
- Identification of ADAR1i-124: The first effective A-to-I RNA editing inhibitor with promising cancer therapeutic potential.iScience · 2026Article
- Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: metabolic vulnerabilities and therapeutic targeting.Molecular cancer · 2025Review
- Metformin Prevents Tumor Cell Growth and Invasion of Human Hormone Receptor-Positive Breast Cancer (HR+ BC) Cells viaInternational journal of molecular sciences · 2024Article
- ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer.International journal of molecular sciences · 2024Review
- Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells.International journal of molecular sciences · 2023Article
- 8-azaadenosine and 8-chloroadenosine are not selective inhibitors of ADAR.Cancer research communications · 2021Article
- Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine.Journal of hematology & oncology · 2021Article
- Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses.Molecular systems biology · 2021Article
- Natural products and other inhibitors of FEuropean journal of medicinal chemistry · 2020Review
- FUSION-Guided Hypothesis Development Leads to the Identification of N⁶,N⁶-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor.Marine drugs · 2017Article
- A Late G1 Lipid Checkpoint That Is Dysregulated in Clear Cell Renal Carcinoma Cells.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The adenosine analog 8-chloroadenosine has been shown to deplete ATP and inhibit tumor growth in hematological malignancies as well as in lung and breast cancer cell lines. We investigated effects of 8-chloroadenosine on clear cell (cc) renal cell carcinoma (RCC) cell lines. 8-chloroadenosine was effective against ccRCC cell viability in vitro, with IC50 ranging from 2 μM in the most sensitive CAKI-1 to 36 μM in the most resistant RXF-393. Proteomic analysis by reverse-phase protein array revealed that 8-chloroadenosine treatment leads to inhibition of the mTOR pathway. In time-course experiments, 8-chloroadenosine treatment rapidly activated AMPK, measured by AMPK and ACC phosphorylation, and subsequently caused dephosphorylation of p70S6K and ribosomal protein RPS6 in the sensitive cell lines. However, in the resistant cell lines, AMPK activity and the mTOR pathway were unaffected by the treatment. We also noted that the resistant cell lines had elevated basal levels of phospho RPS6 and AKT. Inhibition of PI3K pathway enhanced the efficacy of 8-chloroadenosine across all cell lines. Our observations indicate that 8-chloroadenosine activity is associated with inhibition of the mTOR pathway, and that phospho RPS6 and PI3K pathway activation status may determine resistance. Among solid tumors, RCC is one of the few susceptible to mTOR inhibition. We thus infer that 8-chloroadenosine may be effective in RCC by activating AMPK and inhibiting the mTOR pathway.
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